1. Field of the Invention
This invention is directed to monoclonal antibodies against human glycolipid antigens, hybrid cell lines producing these monoclonal antibodies, and methods of using these monoclonal antibodies.
2. Description of the Background Art
Adenocarcinomas are carcinomas derived from glandular tissue or in which the tumor cells form recognizable glandular structures. There is increasing evidence suggesting that human adenocarcinomas characteristically express fucolipids representing blood group antigens and chemically related structures (Hakomori, Annual Reviews of Immunology, 2: 103-126, 1984). The blood group Y difucosylated hapten is structurally well defined and was first described in ovarian cyst glycoproteins (Lloyd, et al., Proceedings of the National Academy of Sciences, USA, 61: 1470-1477, 1968). Later, in its glycolipid form, this hapten was found to be present also in dog intestine (Smith, et al. Biochimica Biophysica Acta, 338: 171-179, 1975) and in human fetal intestine (Karlsson, et al., Journal of Biological Chemistry, 256: 3512-3524, 1981). More recently, a series of more comples glycolipids with dimeric and trimeric Y determinant structures have been characterized that are more abundant in human erythrocytes of blood group O than of blood group A individuals (Kannagi, et al., Journal of Biological Chemistry, 260: 6410-6415, 1985). This determinant has also been found to be present in human liver adenocarcinoma and as an oligosaccharide in the urine of lactating women.
Numerous monclonal antibodies with anti-Y specific activity have been produced by immunizing mice with human gastric cancer, colon cancer, lung cancer, ovarian carcinoma, and human ovarian teratocarcinoma cells. The accumulation of antigens having the Y determinant has been reported in several human adenocarcinomas using the immunoperoxidase technique. The recently reported association between the Y determinant and the carcinoembrionic antigen enhances the relevancy of Y as a diagnostic marker in epithelial adenocarcinomas (Nichols, et al., Journal of Immunology, 135: 1911-1913, 1985).
Although the presence of the Y determinant has been found in glycolipid associated with adenocarcinomas, it is unlikely that a monoclonal antibody which reacts solely with an epitope on the Y determinant would be clinically useful. This is because even though in a given tumor mass many of the malignant cells may express an antigen containing the Y determinant it is highly probable that a small, but significant, population of malignant cells will not express the Y determinant and, hence, would probably be refractory to immunotherapy centered on the administration of a Y-specific monoclonal antibody. It is these surviving cells which can enable a recurrence of the tumor mass. Thus, a need exists for a monoclonal antibody which is capable of reacting with an epitope present on multiple determinants of various antigens since such a monoclonal antibody would have far greater clinical efficacy by virtue of its ability to bind to many different populations of adenocarcinoma cells.